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Enhanced insulin absorption from sublingual microemulsions: effect of permeation enhancers

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Abstract

Microemulsions of insulin (50 IU/mL) comprising permeation enhancers were formulated for sublingual delivery. Circular dichroism (CD) spectra indicated conformational stability, while chemical stability was confirmed by high-performance liquid chromatography (HPLC). CD spectra of insulin in combination with permeation enhancers revealed attenuation of molar ellipticity at 274 nm in the order TCTP > TC-AOT > TC > TC-NMT > Sol P > insulin solution. The molar ellipticity ratios at 208/222 nm confirmed dissociation of insulin in the microemulsions with the same rank order. Matrix-assisted laser diffraction ionization mass spectra (MALDI) revealed a significant shift in intensity signals towards monomer and dimers with a substantially high ratio of monomers, especially in the presence of the TCTP and TC-AOT. Permeation through porcine sublingual mucosa correlated with the dissociation data. A high correlation between the ratio of molar ellipticity at 208/222 nm and serum glucose levels (r 2 > 0.958) and serum insulin levels (r 2 > 0.952) strongly suggests the role of dissociation of insulin on enhanced absorption. While all microemulsions revealed a reduction in serum glucose levels and increase in serum insulin levels, significant differences were observed with the TCTP and TC-AOT microemulsions. High pharmacological availability >60 % and bioavailability >55 % compared to subcutaneous insulin at a low dose of 2 IU/kg appears highly promising. The data clearly suggests the additional role of the permeation enhancers on dissociation of insulin on enhanced sublingual absorption from the microemulsions.

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Acknowledgments

The authors would like to acknowledge University Grants Commission, Government of India for Grant and Fellowship to Nilam Patil. and USV Ltd. India for the gift sample of rh-insulin. We are also thankful to TIFR, India, for the help in the CD spectra and MALDI-MS study.

Conflict of interest

We do not have a financial relationship with the organization that sponsored the research.

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Authors and Affiliations

  1. Department of Pharmaceutical Science and Technology, Institute of Chemical Technology, Deemed University, Mumbai, 400019, India

    Nilam H. Patil & Padma V. Devarajan

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  1. Nilam H. Patil
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  2. Padma V. Devarajan
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Correspondence to Padma V. Devarajan.

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Patil, N.H., Devarajan, P.V. Enhanced insulin absorption from sublingual microemulsions: effect of permeation enhancers. Drug Deliv. and Transl. Res. 4, 429–438 (2014). https://doi.org/10.1007/s13346-014-0205-z

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